TET 2 promotes anti‐tumor immunity by governing G‐ MDSC s and CD 8 + T‐cell numbers
| Autor: | Irfete S. Fetahu, Guo-Ming Shi, Yujiang Geno Shi, Xin-Yu Zhang, Jia-Bin Cai, Dingailu Ma, Hang Liu, Isabella Iwanicki, Feizhen Wu, Bingjie Wang, Tao Hu, Jiuxing Feng, Li Tan, Shuangqi Li, Haikun Wang |
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| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
biology Chemistry Cell Biochemistry law.invention 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Immune system Immunity law Genetics biology.protein medicine Cancer research Suppressor Cytotoxic T cell Antibody Interleukin 6 Molecular Biology 030217 neurology & neurosurgery CD8 030304 developmental biology |
| Zdroj: | EMBO reports. 21 |
| ISSN: | 1469-3178 1469-221X |
| DOI: | 10.15252/embr.201949425 |
| Popis: | The host immune response is a fundamental mechanism for attenuating cancer progression. Here we report a role for the DNA demethylase and tumor suppressor TET2 in host anti-tumor immunity. Deletion of Tet2 in mice elevates IL-6 levels upon tumor challenge. Elevated IL-6 stimulates immunosuppressive granulocytic myeloid-derived suppressor cells (G-MDSCs), which in turn reduce CD8+ T cells upon tumor challenge. Consequently, systematic knockout of Tet2 in mice leads to accelerated syngeneic tumor growth, which is constrained by anti-PD-1 blockade. Removal of G-MDSCs by the anti-mouse Ly6g antibodies restores CD8+ T-cell numbers in Tet2-/- mice and reboots their anti-tumor activity. Importantly, anti-IL-6 antibody treatment blocks the expansion of G-MDSCs and inhibits syngeneic tumor growth. Collectively, these findings reveal a TET2-mediated IL-6/G-MDSCs/CD8+ T-cell immune response cascade that safeguards host adaptive anti-tumor immunity, offering a cell non-autonomous mechanism of TET2 for tumor suppression. |
| Databáze: | OpenAIRE |
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